Peripherally acting anti-CGRP monoclonal antibodies attenuate cortical resting-state connectivity in migraine patients

Background: In about half of migraine patients, anti-calcitonin gene-related peptide monoclonal antibodies reduce monthly migraine days by >50%. In these patients, this class of drugs may change cortical functions by decreasing nociceptive afferent barrage. This prospective study investigated functional connectivity changes in treatment responders after three-month treatment with galcanezumab. Methods: Resting-state functional magnetic resonance imaging data were acquired for patients with high-frequency episodic or chronic migraine (N = 36) before and after treatment. Of these, 19 patients were classified as treatment responders (≥50% reduction in monthly migraine days) and 17 were considered non-responders (<50% reduction). Functional connectivity across cortical regions was assessed using a region-of-interest (ROI)-to-ROI analysis approach. Results: At baseline, there were no significant differences between treatment responders and treatment non-responders. In the treatment responder group, reduced functional connectivity was observed after treatment between regions of the primary somatosensory and motor cortices, insula, and several occipital and temporo-occipital areas (within the visual network). In contrast, no such changes were seen in the non-responder group. Conclusion: These findings suggest that even a relatively short period of reduced nociceptive signals may be sufficient to initiate a cortical recovery process in which its resting hyperexcitable mode shifts to a less excitable state.